1. Field of the Invention
The present invention relates to a novel method for screening an anti-HIV drug, and more specifically relates to an in vivo method for screening an inhibitor against the interaction between SOCS1 and HIV-1 Gag. Furthermore, the present invention relates to a new diagnostic method of AIDS.
2. Related Background of the Invention
There are evidences that 1% of the whole world population has already infected with Human immunodeficiency virus (HIV), and the infection is still spreading steadily. At present, the number of persons infected with the pathogenic virus, HIV, has exceeded 40,000,000 all over the world, and about 5,000,000 persons are being newly infected every year. Probably because the number of persons infected with HIV and AIDS patients in Japan is less than that in European and American countries, no sufficient educational effect is attained and increase of the infected patients is exceptionally still not halted among the developed nations in the world. Though life prognoses of the patients have been improved by the establishment of a recent HAART, the number of patients under long-term medical treatment has increased, and problems of resistance to conventional drugs and new complications such as Immune Reconstitution Syndrome have appeared. In addition, complications with the other chronic infectious diseases including HCV are becoming big social problems together with the issue of HIV-tainted blood products in Japan. It is therefore becoming increasingly important and urgent to respond to the social demand for the elucidation of the mechanisms of persistent viral infection and pathogeny and take effective measures.
The interaction between host protein and HIV protein is essential for the formation of HIV infection, and the interaction itself plays an important role in the growth, life cycle and pathogenic expression mechanism of the virus. In addition, it is necessary to thoroughly understand qualitative, temporal and spatial relationships for the formation of virus-host protein interaction as one of intracellular immune response mechanism of a host individual against virus accompanied by the infection. However, in studies up to now efforts have been focused on the analysis of viral gene structure and the existing anti-AIDS drugs are mainly those targeting HIV protein. A big problem for the current treatment of HIV/AIDS patients is the appearance of drug-resistant viruses, but this problem remains unsolved as long as the easily variable HIV proteins are targeted. To overcome these problems, it is expected to develop drugs that inhibit host factors crucial for HIV replication.
The screening method targeting the above-mentioned host-side factors includes a screening system which inhibits binding of one of HIV-1 genome-encoded accessory proteins Nef with Hck (a host-side factor) (Non-patent document No. 1).
Furthermore, a method for screening an anti-HIV-1 drug comprising culturing “macrophage lineage cells expressing M-CSF receptor, and Nef-ER fusion protein prepared by the fusion of hormone-binding domain of HIV-1 Nef protein and an estrogen receptor which multiply depending on M-CSF” in the presence of an estrogen derivative, M-CSF and a candidate agent to increase the macrophage lineage cell and comparing cell growth of the macrophage lineage cell with that of macrophage lineage cell in the absent of candidate agent is known(Patent document No. 1).
In addition, as an HIV therapy, it has become possible to delay the onset of the disease through the HAART which combines reverse transcriptase inhibitors such as azidothymidine (AZT) with 2-4 protease inhibitors. However, by the appearance of a resistant virus and through adverse reactions, these drugs often have their limits in therapeutic effects.
Therefore, under the circumstances there is an urgent need to develop an anti-AIDS drug with a new action mechanism, targeting the host-side factors.
(Patent documents Nos. 2 and 3)
    [Non-patent document No. 1] Murakami Y, Fukazawa H, Kobatake T, et al. A mammalian two-hybrid screening system for inhibitors of interaction between HIV Nef and the cellular tyrosine kinase Hck. Antiviral Res. 2002; 55:161-168.    [Patent document No. 1] Japanese publication of unexamined patent application No. 2006-129726    [Patent documents No. 2] Japanese publication of unexamined patent application No.2006-262749    [Patent documents No. 3] Japanese publication of unexamined patent application No.2007-312617